Diabetes mellitus encompases a range of conditions characterized by an elevation of blood glucose level, and is divided into two principal varieties. Type 1 accounts for less than 10% of all diabetics and is due to an autoimmune attack on the pancreatic β-cells that results in their destruction. Type 2 diabetics exhibit impairments of both insulin secretion and insulin action. Type 2 diabetes has reached epidemic proportions in Western societies, and is predicted to affect 300 million people worldwide by 2025. Nearly 800,000 new cases of diabetes mellitus are diagnosed per year in the United States, and approximately 15% of patients will develop a lower extremity ulceration at some point in their lives. It has been estimated that up to 2 million Americans suffer from non-healing lower extremity wounds, accounting for 162,500 annual hospitalizations and one billion dollars per year in health care costs in the United States.
The pathophysiology of diabetic lower extremity ulcerations and delayed healing has been well described. Contributing factors include progressive development of asensory, vasomotor and autonomic neuropathy leading to loss of protective sensation, joint and bone deformities that increase plantar foot pressure, and alterations in autoregulation of dermal blood flow. Diabetics show earlier development and progression of lower extremity peripheral arterial occlusive disease (PAD) with a predilection for the trifurcation level of vessels just distal to the knee. In addition, the tissue microcirculation is severely diseased (microangiopathy) even in patients with patent proximal vessels. Some of these vascular complications as well as the healing defects, in diabetes, have been associated with a decrease in number and function of circulating BMD EPC. Impaired host responses to infection and other cellular dysfunctions also contribute to the refractory nature of diabetic wounds. About 20% of diabetic lower extremity ulcers have arterial flow insufficiency as their primary etiology, approximately 50% will have primary diabetic neuropathy, and about 30% will have both conditions.
Despite a multidisciplinary approach (associating glycemia control, daily local care, foot off-loading antibiotic therapy, and surgical revascularization), treatment of diabetic ulcers is often prolonged, intensive and costly and treatment failures are common. Current approaches include debridement, frequent changes of wound dressing, specially fitted footwear, oral or intravenous antibiotics, complete bed rest, lengthy hospitalization and surgical revascularization. Ulcer-related complications can in some cases require amputation. Therefore, there is a need for treatments which accelerate the rate of the healing of chronic dermal skin ulcers in general, and of diabetic ulcers, in particular.